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Human TopBP1 localization to the mitotic centrosome mediates mitotic progression

Title
Human TopBP1 localization to the mitotic centrosome mediates mitotic progression
Authors
Bang S.W.Ko M.J.Kang S.Kim G.S.Kang D.Lee J.Hwang D.S.
Ewha Authors
강동민
SCOPUS Author ID
강동민scopus
Issue Date
2011
Journal Title
Experimental Cell Research
ISSN
0014-4827JCR Link
Citation
vol. 317, no. 7, pp. 994 - 1004
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
TopBP1 contains repeats of the BRCA1 C-terminal (BRCT) domain and plays important roles in DNA damage response, DNA replication, and other cellular regulatory functions during the interphase. In prometaphase, metaphase, and anaphase, TopBP1 localizes to the mitotic centrosomes, which function as spindle-poles for the bipolar separation of sister chromatids. The localization of TopBP1 to the mitotic centrosomes is mediated by amino acid residues 1259 to 1420 in the TopBP1 C-terminal region (TbpCtr). GST and DsRed2 tags fused to TbpCtr were localized in the mitotic centrosomes, thereby suggesting that TbpCtr functions as a mitosis-specific centrosome localization signal (CLS). Mutations of Ser 1273 and/or Lys 1317, which were predicted to interact with a putative phosphoprotein, inhibited CLS function. Ectopic expression of TbpCtr specifically eliminated endogenous TopBP1 from the mitotic centrosomes, whereas mutant TbpCtr derivatives, containing substitutions at Ser 1273 and/or Lys 1317, did not. The specific elimination of TopBP1 from the mitotic centrosomes prolonged the durations of prometaphase and metaphase and shortened the inter-kinetochore distances of metaphase sister chromatids while maintaining the spindle assembly checkpoint. These results suggest that the localization of TopBP1 to the mitotic centrosomes is necessary for proper mitotic progression. © 2011 Elsevier Inc.
DOI
10.1016/j.yexcr.2011.01.022
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자연과학대학 > 생명과학전공 > Journal papers
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